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1. 发明授权

US08044206B2 Nitrogen—containing heterocyclic derivatives having 2,6-disubstituted styryl 失效
标题翻译：含2,6-二取代苯乙烯基的含氮杂环衍生物
公开(公告)号：US08044206B2
公开(公告)日：2011-10-25
申请号：US10548197
申请日：2004-03-05
申请人： Kazumi Kikuchi , Makoto Oku , Jiro Fujiyasu , Norio Asai , Toshihiro Watanabe , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
发明人： Kazumi Kikuchi , Makoto Oku , Jiro Fujiyasu , Norio Asai , Toshihiro Watanabe , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
IPC分类号： C07D211/08 , A61K31/47
CPC分类号： C07D211/12
摘要： The invention provides a novel nitrogen-containing heterocyclic derivative having 2,6-disubstituted styryl and a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the nitrogen-containing heterocyclic derivative and a pharmaceutically acceptable salt thereof, in particular, a pharmaceutical composition effective as a sodium channel inhibitor, having an excellent analgesic action especially on neuropathic pain with minimized side effects.
摘要翻译：本发明提供了具有2,6-二取代苯乙烯基的新型含氮杂环衍生物及其药学上可接受的盐，以及包含含氮杂环衍生物及其药学上可接受的盐的药物组合物，特别是作为钠通道抑制剂，具有优异的镇痛作用，特别是对神经性疼痛具有最小的副作用。

2. 发明申请

US20080070898A1 Piperidine Derivative or Pharmaceutically Acceptable Salt Thereof 审中-公开
标题翻译：哌啶衍生物或其药学上可接受的盐
公开(公告)号：US20080070898A1
公开(公告)日：2008-03-20
申请号：US11661446
申请日：2005-08-31
申请人： Kazumi Kikuchi , Jiro Fujiyasu , Toshihiro Watanabe , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
发明人： Kazumi Kikuchi , Jiro Fujiyasu , Toshihiro Watanabe , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
IPC分类号： A61K31/5377 , A61K31/496 , A61K31/553 , A61P25/04 , C07D273/01 , C07D401/06 , C07D413/06
CPC分类号： C07D211/16 , C07D211/18 , C07D211/22 , C07D211/26 , C07D211/34 , C07D211/46 , C07D401/12 , C07D405/12 , C07D413/12 , C07D487/08 , C07D491/10
摘要： The piperidine derivative of the present invention in which the 4-position of the piperidine ring is bonded, via vinylene, to a mono-substituted (—R1) or unsubstituted benzene ring and the 1-position of the piperidine ring has an acyl group [—C(═O)—R4], or a pharmaceutically acceptable salt thereof has an excellent sodium channel inhibition action and an excellent analgesic action and shows a high analgesic effect particularly to neurogenic pain. The present compound is useful as a sodium channel inhibitor of low side effect
摘要翻译：其中哌啶环的4位通过亚乙烯基键合到单取代的（-R 1）或未取代的苯环上的本发明的哌啶衍生物和1-取代的哌啶环具有酰基[-C（-O）-R 4]，或其药学上可接受的盐具有优异的钠通道抑制作用和优异的镇痛作用，并显示出高镇痛作用特别是神经源性疼痛。本发明化合物可用作低副作用的钠通道抑制剂

3. 发明申请

US20070099956A1 Nitrogen-containing heterocyclic derivatives having 2, 6-disubstituted styryl 失效
标题翻译：含2,6-二取代苯乙烯基的含氮杂环衍生物
公开(公告)号：US20070099956A1
公开(公告)日：2007-05-03
申请号：US10548197
申请日：2004-03-05
申请人： Kazumi Kikuchi , Makoto Oku , Jiro Fujiyasu , Norio Asai , Toshihiro Watana , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
发明人： Kazumi Kikuchi , Makoto Oku , Jiro Fujiyasu , Norio Asai , Toshihiro Watana , Yukinori Nagakura , Hiroshi Tomiyama , Motoharu Sonegawa , Kazuo Tokuzaki , Yoshinori Iwai
IPC分类号： A61K31/47 , A61K31/44 , C07D215/12 , C07D213/81
CPC分类号： C07D211/12
摘要： The invention provides a novel nitrogen-containing heterocyclic derivative having 2,6-disubstituted styryl and a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the nitrogen-containing heterocyclic derivative and a pharmaceutically acceptable salt thereof, in particular, a pharmaceutical composition effective as a sodium channel inhibitor, having an excellent analgesic action especially on neuropathic pain with minimized side effects.
摘要翻译：本发明提供了具有2,6-二取代苯乙烯基的新型含氮杂环衍生物及其药学上可接受的盐，以及包含含氮杂环衍生物及其药学上可接受的盐的药物组合物，特别是作为钠通道抑制剂，具有优异的镇痛作用，特别是对神经性疼痛具有最小的副作用。

4. 发明申请

US20110171192A1 SUBSTITUTED AMINE DERIVATIVE AND MEDICINAL COMPOSITION COMPRISING SAME AS THE ACTIVE INGREDIENT 审中-公开
标题翻译：取代的胺衍生物和药物组合物作为活性成分包含
公开(公告)号：US20110171192A1
公开(公告)日：2011-07-14
申请号：US12737925
申请日：2009-08-27
申请人： Hiroshi Tomiyama , Kazuo Tokuzaki , Yoshinori Iwai
发明人： Hiroshi Tomiyama , Kazuo Tokuzaki , Yoshinori Iwai
IPC分类号： A61K31/7064 , C07H19/14 , A61K38/44 , A61P3/00 , A61P13/00 , A61P13/12 , A61P29/00 , A61P3/06 , A61P3/04 , A61P3/10 , A61P7/00 , A61P37/06 , A61P9/12 , A61P11/00
CPC分类号： C07D239/70 , A61K31/517 , A61K31/519 , A61K31/7042 , A61K45/06 , C07D409/04 , C07D487/04 , C07H19/14 , A61K2300/00
摘要： A compound represented by following general formula (I): wherein, represents a single bond or a double bond; L represents —NH— or the like; X1 represents N or C, provided that in the case where X1 is N, X2 represents C—R and in the case where X1 is C, X2 represents N—R1 or the like; Y's may be either the same or different and represent CH2 or the like; A represents a non-natural sugar residue represented by following general formula: wherein, m represents 0 to 1; represents a single bond or a double bond; X represents O or the like; R3 to R8 may be either the same or different and represent hydroxy group or the like; and B represents a group represented by following general formula: wherein, n and k represent 0 to 5; represents a single bond or a double bond; Z1 to Z16 may be either the same or different and represent CH or the like; R10 and R11 may be either the same or different and represent a lower alkoxy group having 1 to 5 carbon atoms or the like; and R15 represents a hydrogen atom or the like, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or solvate thereof. Because of having an excellent CNT2 inhibitory activity and showing a high in vivo stability and stable physicochemical properties, the aforesaid compound is useful as a remedy for hyperuricemia.
摘要翻译：由以下通式（I）表示的化合物：其中，表示单键或双键; L表示-NH-等; X1表示N或C，条件是在X1为N的情况下，X2表示C-R，在X1为C的情况下，X2表示N-R1等; Y可以相同或不同，表示CH2等; A表示由以下通式表示的非天然糖残基：其中，m表示0至1; 代表单键或双键; X表示O等; R3至R8可以相同或不同，表示羟基等; 并且B表示由以下通式表示的基团：其中，n和k表示0至5; 代表单键或双键; Z1至Z16可以相同或不同，表示CH等; R 10和R 11可以相同或不同，表示具有1〜5个碳原子的低级烷氧基等; R 15表示氢原子等，其药学上可接受的盐，前药，其水合物或其溶剂合物。由于具有优异的CNT2抑制活性并且具有高的体内稳定性和稳定的物理化学性质，上述化合物可用作高尿酸血症的补救剂。

5. 发明申请

US20080119441A1 Phosphonic Acid Derivatives and the Treating Agents of Diseases Related Hyperphosphatemia 失效
标题翻译：膦酸衍生物和相关高磷酸盐血症的治疗药物
公开(公告)号：US20080119441A1
公开(公告)日：2008-05-22
申请号：US11664830
申请日：2005-10-05
申请人： Hiroshi Tomiyama , Masayuki Yokota , Kazuo Tokuzaki , Ryoko Tomita
发明人： Hiroshi Tomiyama , Masayuki Yokota , Kazuo Tokuzaki , Ryoko Tomita
IPC分类号： A61K31/675 , A61K31/66 , C07F9/06 , C07F9/22
CPC分类号： C07F9/6541 , C07F9/3834 , C07F9/3882 , C07F9/3891 , C07F9/59 , C07F9/6539 , C07F9/65517 , C07F9/655345 , C07F9/655354 , C07F9/6558 , C07F9/65586
摘要： This invention related to a series of new phosphonic acid derivatives having anti-hyperphosphatemia activity. (I)[wherein: A is selected from —(CH2)n—, —CO—, —(CH2)n—CO—(CH2)m—, —(CH2)n—CS—(CH2)m— or branched alkylene group. B ring and C ring are selected from benzene ring, naphthalene ring, azulene ring or, heterocycle or fused heterocycle. D is —(CH2)(n+1)—, —(CH2)-O—(CH2)m—, —(CH2)—S(O)o—(CH2)m—, —CF3 or —(CH2)n—NR10—(CH2)m— (wherein: D ring is connected with the carbon atom composing C ring.) E is selected from oxygen atom or sulfur atom. P is phosphine atom. R1˜R7 (wherein R1 and R2, R4 and R5 are joined together with neighbored carbon atom to form 5˜7 membered saturated or unsaturated hydrocarbon ring, or 5˜6 membered fused heterocycle. R1, R2 and R3 are not hydrogen atom if B ring is benzene ring.) may be the same or different and are substituents. R8 and R9 are may be the same or different and are substituents. R10 is alkyl group. n and m are 0-10. o is 0-2.
摘要翻译：本发明涉及一系列具有抗高磷酸血症活性的新型膦酸衍生物。（I）[其中：A选自 - （CH 2）n - ， - CO - ， - （CH 2 H 2）（CH 2）n - ， - （CH 2）n - ， - （CH 2 CH 2）n - -C（ - ） - （CH 2 CH 2）m - 或支链亚烷基。 B环和C环选自苯环，萘环，薁环或杂环或稠合杂环。 D是 - （CH 2）2（n + 1） - ， - （CH 2）-O-（CH 2 CH 2）m - （CH 2） - （CH 2）n - （CH 2）m - / > - ， - CF 3 - 或 - （CH 2）n - NR 10 - （CH 3） 2）其中：D环与构成C环的碳原子连接。）E选自氧原子或硫原子。 P是膦原子。（其中R 1和R 2，R 4，R 4，R 4， R 5与邻位的碳原子连接在一起形成5〜7元饱和或不饱和烃环，或5〜6元稠合杂环，R 1，R 2， > 2和R 3不是氢原子，如果B环是苯环）可以相同或不同，并且是取代基。 R 8和R 9可以相同或不同，并且是取代基。 R 10是烷基。 n和m为0-10。 o是0-2。

6. 发明授权

US07691898B2 Phosphonic acid derivatives and the treating agents of diseases related hyperphosphatemia 失效
标题翻译：膦酸衍生物和疾病相关高磷血症的治疗剂
公开(公告)号：US07691898B2
公开(公告)日：2010-04-06
申请号：US11664830
申请日：2005-10-05
申请人： Hiroshi Tomiyama , Masayuki Yokota , Kazuo Tokuzaki , Ryoko Tomita
发明人： Hiroshi Tomiyama , Masayuki Yokota , Kazuo Tokuzaki , Ryoko Tomita
IPC分类号： A61K31/381 , C07D333/46 , C07F9/30
CPC分类号： C07F9/6541 , C07F9/3834 , C07F9/3882 , C07F9/3891 , C07F9/59 , C07F9/6539 , C07F9/65517 , C07F9/655345 , C07F9/655354 , C07F9/6558 , C07F9/65586
摘要： This invention related to a series of new phosphonic acid derivatives having anti-hyperphosphatemia activity. wherein: A is selected from —(CH2)n—, —CO—, —(CH2)n—CO—(CH2)m—, —(CH2)n—CS—(CH2)m— or a branched alkylene group, B ring and C ring are selected from a benzene ring, naphthalene ring, azulene ring or, heterocycle or fused heterocycle compound, D is —(CH2)(n+1)—, —(CH2)—O—(CH2)m—, —(CH2)—S(O)o—(CH2)m—, —CF3 or —(CH2)n—NR10—(CH2)m— wherein a D ring is connected with the carbon atom composing the C ring, E is selected from an oxygen atom or a sulfur atom, P is a phosphine atom, R1˜R7, wherein R1 and R2, R4 and R5 are joined together with neighbored carbon atom to form 5˜7 membered saturated or unsaturated hydrocarbon ring, or 5˜6 membered fused heterocycle, R1, R2 and R3 are not a hydrogen atom if the B ring is a benzene ring and may be the same or different and are substituents, R8 and R9 are may be the same or different and are substituents, R10 is an alkyl group, n and m are 0-10 and o is 0-2.
摘要翻译：本发明涉及一系列具有抗高磷酸血症活性的新型膦酸衍生物。其中：A选自 - （CH 2）n - ， - CO - ， - （CH 2）n -CO-（CH 2）m - ， - （CH 2）n -C CS-（CH 2）m-或支链亚烷基， B环和C环选自苯环，萘环，薁环或杂环或稠合杂环化合物，D是 - （CH 2）（n + 1） - ， - （CH 2）-O-（CH 2）m - ， - （CH2）-S（O）o-（CH2）m-，-CF3或 - （CH2）n-NR10-（CH2）m-，其中D环与构成C环的碳原子连接，E 选自氧原子或硫原子，P为膦原子，R1〜R7，其中R1和R2，R4和R5与邻位碳原子连接在一起形成5〜7元饱和或不饱和烃环，或5 如果B环是苯环并且可以相同或不同，并且是取代基，则R 6，R 6和R 3不是氢原子，R 8和R 9可以相同或不同，并且是取代基R 10 是烷基，n和m是0-10，o是0-2。

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